TY - JOUR
T1 - Characterization of functional transposable element enhancers in acute myeloid leukemia
AU - Zeng, Yingying
AU - Cao, Yaqiang
AU - Halevy, Rivka Sukenik
AU - Nguyen, Picard
AU - Liu, Denghui
AU - Zhang, Xiaoli
AU - Ahituv, Nadav
AU - Han, Jing Dong J.
N1 - Publisher Copyright:
© 2020, Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Transposable elements (TEs) have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes. Acute myeloid leukemia (AML) develops as a consequence of a series of genetic changes in hematopoietic precursor cells, including mutations in epigenetic factors. Here, we set out to study the gene regulatory role of TEs in AML. We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data. We show that a large number of TEs in general, and more specifically mammalian-wide interspersed repeats (MIRs), are more enriched in AML cells than in normal blood cells. We obtained a similar finding when analyzing histone modification data in AML patients. Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis. To functionally validate their regulatory role, we selected 19 MIR regions in AML cells, and tested them for enhancer activity in an AML cell line (Kasumi-1) and a chronic myeloid leukemia (CML) cell line (K562); the results revealed several MIRs to be functional enhancers. Taken together, our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.
AB - Transposable elements (TEs) have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes. Acute myeloid leukemia (AML) develops as a consequence of a series of genetic changes in hematopoietic precursor cells, including mutations in epigenetic factors. Here, we set out to study the gene regulatory role of TEs in AML. We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data. We show that a large number of TEs in general, and more specifically mammalian-wide interspersed repeats (MIRs), are more enriched in AML cells than in normal blood cells. We obtained a similar finding when analyzing histone modification data in AML patients. Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis. To functionally validate their regulatory role, we selected 19 MIR regions in AML cells, and tested them for enhancer activity in an AML cell line (Kasumi-1) and a chronic myeloid leukemia (CML) cell line (K562); the results revealed several MIRs to be functional enhancers. Taken together, our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.
KW - MIR
KW - acute myeloid leukemia
KW - enhancer
KW - promoter
KW - transposable element
UR - http://www.scopus.com/inward/record.url?scp=85082134834&partnerID=8YFLogxK
U2 - 10.1007/s11427-019-1574-x
DO - 10.1007/s11427-019-1574-x
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 32170627
AN - SCOPUS:85082134834
SN - 1674-7305
VL - 63
SP - 675
EP - 687
JO - Science China Life Sciences
JF - Science China Life Sciences
IS - 5
ER -